Note: Descriptions are shown in the official language in which they were submitted.
CA 02319987 2000-09-20
- 1 -
POLYMERIC COMPOSITIONS FOR ION-SELECTIVE ELECTRODES
FIELD OF THE INVENTION
The present invention is broadly directed to ion-
selective electrodes (ISE's). More specifically, it
relates to polymeric compositions for internal reference
electrodes of dry-operative ISE's.
BACKGROUND OF THE INVENTION
A wide variety of ion-selective electrodes are
is known for measuring the amount of an ion in solution.
Typically devices for obtaining such measurements
include a reference or standard electrode and a separate
ion-selective electrode. When simultaneously contacting
a solution to be analyzed, the reference or standard
electrode and the ion-selective electrode together
constitute an electrochemical cell across which a
potential difference develops in proportion to the
logarithm of the activity of the ion to which the ion-
selective electrode is sensitive. The activity is
related to the concentration of the ibn in the solution.
The relationship between potential difference and ion
activity in solution is described by the well-known
Nernst equation. An electrometric device, usually
either a direct reading circuit or a null-balance
CDS-18
CA 02319987 2000-09-20
- 2 -
potentiometric circuit, is employed for measuring the
potential between the electrodes.
In principle, an ion-selective electrode can be
constructed which is sensitive to any cationic or
anionic substance. Cations that can be determined
include, but are not limited to, group IA ions, such as
sodium, potassium, lithium (alkali metals) and hydrogen;
group IIA metal ions such as calcium and magnesium
io (alkaline earths); metal ions from groups VIA, VIIA,
VIIIA, IB, IIB and IIIB; and lead ion from group IVB.
Anions include, but are not limited to, halide ions,
chloride and fluoride being of particular interest.
Carbon dioxide, which is non-ionic, can be determined
using an ISE sensitive to hydrogen ion.
Ionic substances are present in a wide range of
sample types, including but not limited to, industrial
effluents, tap water, rain water, sewer water,
biological sources, such as plant and animal derived
fluids, and so forth. Human biological fluids are of
particular interest and include whole blood, serum,
plasma, saliva, sweat, bronchial fluid, vaginal
excretions, and so on.
Electrodes based on ion-selective glass membranes
are well-known. Solid-state electrodes are also known,
such as those described in U.S. Patent 3,856,649 to
CDS-181
CA 02319987 2000-09-20
- 3 -
Genshaw et al. (the '649 patent) and in a paper entitled
"Miniature Solid State Potassium Electrode for Serum
Analysis" in Analytical Chemistry, v45, pp 1782-84
(1973). An advance in solid-state electrodes has been
s achieved with the "dry-operative" electrodes described
in U.S. Patent 4,214,968 to Battaglia et. al. (the '968
patent), U.S. Patent 4,053,381 to Hamblen et al. and
U.S. Patent 4,487,679 to Stare.
io Metal, insoluble metal salt solid-state electrodes
comprise an electrically conductive inner element, a
metal, having disposed thereon an insoluble salt of the
metal. The metal, insoluble metal salt combination
represents a half-cell or in the context of the present
is invention, an internal reference electrode, which can be
used directly by contacting it with a solution
containing an ion to be measured. Alternatively, the
internal reference electrode can comprise in intimate
contact with the metal and insoluble metal salt, a
20 water-soluble salt dispersed in a hydrophilic "binder"
capable of forming a solid matrix. The anion of the
water-soluble salt has the same identity as the anion of
the insoluble metal salt. In intimate contact with the
matrix of the internal reference electrode is a
25 hydrophobic zone which shields the internal reference
electrode from direct contact with the ion-containing
solution. The hydrophobic zone generally comprises an
ion-specific carrier.
CDS-181
CA 02319987 2000-09-20
- 4 -
The 1649 patent describes the use of polyvinyl
alcohol as binder to form a hydrophilic layer which
includes a water-soluble salt.
The '968 patent lists several binders for the "dried"
reference electrolyte solution: polyvinyl alcohol,
gelatin, agarose, deionized gelatin, polyacrylamide,
polyvinyl pyrrolidone, poly(hydroxyethyl acrylate),
poly(hydroxyethyl methacrylate) and poly(acrylic acid).
Deionized gelatin is a preferred binder in the 1968
patent. Unfortunately, in dry-operative ISE's, the layer
comprising the internal reference electrode having gelatin
as binder, is brittle, it does not adhere well to the
hydrophobic overlayer, and is sensitive to variations in
is humidity. As a result, the integrity and performance of
these ISE's are adversely affected.
SUMMARY OF THE INVENTION
We have found that improved dry-operative ion-
selective electrode performance can be achieved using as
binder, copolymers prepared from a hydrophilic monomer
having at least one carboxylic acid group or salt thereof
and a hydrophobic monomer. The resulting copolymer has a
glass transition temperature lower than the acid
homopolymer, provides good interlayer adhesion as well as
high salt tolerance.
CDS-181
= CA 02319987 2000-09-20
- 5 -
In one aspect the present invention relates to dry-
operative ion-selective electrodes comprising:
a) an internal reference electrode
comprising a water-soluble salt dispersed in a polymer
consisting essentially of 60 to 99 weight percent of a
monomer having at least one carboxyl group or salt
thereof and 1 to 40 weight percent of a hydrophobic
monomer; and
b) a hydrophobic zone in contact with
the internal reference electrode, said hydrophobic zone
having distributed therein a carrier selective for the
ion.
The internal reference electrode can be a metal
salt, insoluble metal salt type electrode, or an
oxidatiori-reduction type electrode comprising a metal
and a redox salt couple. The dry-operative ion-
selective electrode may further comprise a support
wherein the internal reference electrode is disposed
between the support and the hydrophobic zone. In
preferred embodiments, the binder polymer comprises 70
to 95 weight percent of a monomer having at least one
carboxyl group or salt thereof and 5 to 30 weight
percent of a hydrophobic monomer.
Preferred polymers of the invention consist
essentially of a monomer of formula
CDS-181
= CA 02319987 2000-09-20
- 6 -
1 3
H R2
wherein Rl is H or -COOM; R2 is H, Cl or -COOM; R3 is
-COOM, -CH2CH2COOM, -CHCONHC (CH3) 2CH2COOM, or
/ \ /CH2COOM
CH2 N
\CH2COOM
; M is H, alkali metal
_ i4
+
R7-i-R5
cation or R6 wherein R4, R5, R6, R, are
independently H, methyl, or ethyl, and a monomer of
formula
Oy Rg
=--~H2 7
Rg
wherein RB is H or methyl; R9 is methoxy, ethoxy,
propoxy, butoxy, hexoxy or -NHCH3.
In another-ampect the present invention relates to
a method for determining the presence or amount of an
ion in a liquid comprising:
CDS-181
CA 02319987 2000-09-20
- 7 -
A) contacting a dry-operative ion-
selective first electrode with a sample of the liquid
wherein the dry-operative first electrode comprises
a) an internal reference
electrode comprising a water-soluble salt dispersed in a
polymer consisting essentially of 60 to 99 weight percent
of a monomer having at least one carboxyl group or salt
thereof and 1 to 40 weight percent of a hydrophobic
monomer; and
b) a hydrophobic zone in
contact with the internal reference electrode, said
hydrophobic zone having distributed therein a carrier
selective for the ion,
B) contacting a second electrode with a
solution comprising a known or constant amount of an ion
to which said second electrode is selective, and wherein
said dry-operative first electrode and said second
electrode are in electrochemical contact or are capable
of being in electrochemical contact; or
C) contacting the dry-operative ion-
selective first electrode and the second electrode with
the same sample of the.liquid wherein the sample
comprises a known or constant amount of an ion to which
said second electrode is selective; and
CDS-181
CA 02319987 2000-09-20
- 8 -
D) measuring the potential difference
between the dry-operative first electrode and the second
electrode as a determination of the presence or amount
of the ion in the liquid sample.
The second electrode in the above method of
determining an ion can be any suitable reference
electrode, such as a calomel electrode or others known
in the art, or a solid-state electrode, such as a dry-
io operative electrode. It can be identical in structure
and composition to the dry-operative ion-selective first
electrode. If the first and second electrodes are
selective for the same type of ion then the solution of
part B comprises a known or constant amount of said ion.
If the second electrode is selective for a second ion
type that is different from that to which the first
electrode is selective, then the solution comprises the
second ion type in a known or constant amount. If the
method for determining the presence or amount of an ion
is conducted as in part C, then the sample comprises a
known or constant amount of a second iori to which the
second electrode is selective and which is different
from the ion to which the first electrode is selective.
DETAILED DESCRIPTION OF THE INVENTION
As ISE technology is well-known and described in
numerous publications, only a brief account of the
CDS-181
CA 02319987 2000-09-20
- 9 -
construction and use of dry-operative electrodes will be
provided. Specific details can be found, for instance, in
U.S. Patents 4,214,968, 4,053,381 and 4,487,679. The
invention is illustrated by reference to a preferred
embodiment, a metal, insoluble metal salt type electrode.
However, the invention is not limited to this type of
electrode.
The internal reference electrode can comprise any
metal that is commonly used for this purpose; preferably
one that readily forms an insoluble salt and has good
electrical properties. Such metals include silver,
copper, lead, amalgams and the like. The insoluble salt
is disposed on a surface portion of the metal and has, as
cation, the cation form of the metal. The anion of the
insoluble salt is generally a halide or a sulfide. The
insoluble salt may be formed by anodizing the metal in a
suitable solutiori, by a physical application of a
dispersion of the salt in a suitable carrier that will
adhere to the metal or by other suitable methods. The
salt may be formed about an end portion'of the metal or
its position may be varied according to the desired
structural features of the electrode. The water-soluble
salt is in intimate contact with the metal and insoluble
metal salt. It generally has as cation, an alkali or
alkaline earth metal, such as sodium, potassium,
magnesium, calcium, and barium; and as anion, a halide.
Representative salts include but are not limited to NaCl,
CDS-181
CA 02319987 2000-09-20
- 10 -
KC1, KBr, MgC12, and BaC12. The water-soluble salt is
dispersed in a solid-forming hydrophilic binder, as
discussed above. In contact with the binder is a
hydrophobic zone. The hydrophobic zone can be formed from
s any suitable hydrophobic polymeric material such as
polyvinyl chloride (PVC),polyvinyl acetate,
polymethylmethacrylate, polyvinylidene chloride,
polystyrene and the like. An ion-selective carrier
dispersed in the hydrophobic zone renders the electrode
io specific for an ion of choice. A large number of carriers
selective for specific ions are known, including but not
limited to: valinomycin, which is selective for potassium;
cyclic polyethers of various constitution which make the
electrode selective for lithium, rubidium, potassium,
15 cesium or sodium ions; tetralactones; biscyclic ethers;
cryptands; hemispherands; calixarenes; cyclic amides;
macrolide act-ins(monactin, nonactin, dinactin, trinactin),
the enniatin group (enniatin A,B), cyclohexadepsipeptides,
- gramicidine, nigericin, dianemycin, nystatin, monensin,
20 esters of monensin (especially methyl monensin for sodium
ion), antamanide, and alamethicin (cyclic polypeptides);
magnesium or zinc uranyl acetate; 6,8-dichlorobenzoylene
urea; didecylphosphoric acid-dioctyl phenylphosphonate;
tetraphenylboron; tridodecylhexadecylammonium nitrate; and
25 4-amino-4'-chlorodiphenylhydrochloride barium salt. Other
useful carriers are described by Amman et al. in Helv.
Chim. Acta, v58, p535 (1975). Useful calcium ion
selective electrodes can be prepared using antibiotic A-
CDS-181
CA 02319987 2000-09-20
- 11 -
23187 as the ion carrier and tris(2-ethyl hexyl)
phosphate, tri(m-tolyl)phosphate, or dioctyl phenyl
phosphonate as the carrier solvent. (See Pressman, B. C.,
Annual Review of Biochemistry, E. B. Snell, ed., V5, 1976,
pp. 501-503). Thus, electrodes can be prepared which are
selective for potassium ion, sodium ion, lithium ion,
magnesium ion, calcium ion, ammonium ion, hydrogen ion,
cesium ion, bromide ion, chloride ion, fluoride ion, or
iodide ion, carbonate ion, salicylate ion, nitrate ion,
and so forth.
In preferred embodiments the ion-selective
electrodes of the invention are multilayered and include
a support which may be comprised of any suitable
material, such as ceramic, wood, glass, metal, paper or
cast, extruded or molded plastic or polymeric materials,
and so on.
The presence or amount of an ion in a solution can
be determined by measuring the difference in electrical
potential (potential difference) between solution 1 and
solution 2 (both usually aqueous) in a cell arrangement
schematically represented by the following:
zs electrode 1/solution 1//solution 2/electrode 2
The activity or concentration of the ion of
interest in solution 2 (in this case, the solution of
CDS-181
CA 02319987 2000-09-20
- 12 -
unknown concentration) can be derived.from the measured
potential difference through use of the well-known
Nernst equation. Alternatively, any algorithm or method
relating the measured potential difference to the amount
or effective amount of the ion can be used. Electrode 2
can be a dry-operative ion-selective electrode of the
present invention. Electrode 1 can be any suitable
reference electrode or standard electrode such as a
saturated calomel electrode. It can be a dry-operative
ISE of the present invention. Solution 1 can comprise a
known amount of the ion whose activity or amount is
unknown in solution 2.
The activity or amount of an ion can also can also be
is determined by measuring the potential difference between
two electrodes contacting a single solution containing the
ion using a so-called junctionless arrangement represented
by the following:
electrode 1/solution/electrode 2
wherein electrode 1 is an ion-selective electrode specific
for an ion in the solution. Electrode 2 can be a
reference electrode or an ion-selective electrode specific
for a different ionic species which is present at a known
or constant level in the solution.
CDS-181
CA 02319987 2000-09-20
- 13 -
EXAMPLES
The polymeric binders of the present invention can be
prepared from hydrophilic vinyl addition carboxylic acid
monomers or salts thereof including: acrylic acid,
methacrylic acid, alpha methyl maleic acid, maleic acid,
chlorofumaric acid, fumaric acid, N-(meta-
vinylbenzyl)iminodiacetic acid, N-(para-
vinylbenzyl)iminodiacetic acid, alpha-chloroacrylic acid,
io mono-methyl fumarate, 3-acrylamido-3-methylbutanoic acid,
and alpha-methylene glutaric acid, and hydrophobic
monomers such as, methyl acrylic acid, ethyl acrylic acid,
butyl acrylate, propyl acrylate, hexyl acrylate and their
methacrylate homologs plus hetero alkyl acrylate and
is methacrylamides.
Preferred copolymers of the present invention include
the carboxylic acid monomers in an amount ranging from 60
to 99 percent by weight, more preferably about 70 to 95
20 percent by weight. The hydrophobic monomers are present
in an amount ranging from 1 to 40, and more preferably 5
to 3'0 percent by weight. The monomers may or may not be
crosslinkable as described in U.S. Patent 4,283,504. The
binder polymers of the invention are soluble in aqueous
25 solution wherein the pH is greater than or equal to about
pH 5.0, and are insoluble or poorly soluble in organic
solvents such as 2-butanone and tetrahydrofuran. Organic
solvents are used to dissolve the hydrophobic polymers
comprising the hydrophobic zone of the ISE. For
CDS-181
CA 02319987 2000-09-20
- 14 -
multilayer ISE's the polymers should be capable of
maintaining their structural integrity as an intact layer
when over-coated with a hydrophobic polymer coated from an
organic solvent.
The polymers of the present invention can be made
using well-known polymerization techniques, such as a
solution or dope polymerization method in the presence of
a suitable catalyst. After the reaction has proceeded
for a desired time, the product may be precipitated by
pouring the reaction mass into water, washing the
precipitate and redissolving it in water containing a
suitable hydroxide salt. Emulsion polymerization or
other methods, known to those skilled in the art, may
also be used. A particular relative amount of carboxylic
acid monomer to hydrophobic monomer in the polymer can be
obtained by using that particular relative amount of the
vinyl addition monomers at the start of the
polymerization. The preparation and use of copolymers of
acrylic acid and alkyl acrylates for photographic
systems are described in U.S. Patents 3,062,674 and
3,220,844 both to Houck et al.
The following example illustrates the preparation of
a preferred polymer, poly(ethyl acrylic acid-co-acrylic
acid (weight ratio 10/90), hereinafter, Polymer A.
CDS-181
CA 02319987 2000-09-20
- 15 -
Example 1
Prepara ti on of Polymer A
To a five liter round bottom flask equipped with a
stirrer (air-driven teflon paddle on a glass shaft), argon
s gas inlet, and a condenser, was added 3.6kg deionized,
distilled water which was brought to 70 C and sparged with
argon gas for 10 min. To this aqueous solution was added,
with continual stirring, 360g of acrylic acid and 40g of
ethyl acrylic acid. After 10 min, 4.Og of ammonium
persulfate dissolved in lOmL water was added to the
mixture. The reaction was maintained at 70 C under argon
for 15 hrs. The solids content was 10.6% (weight/weight,
w/w). The solution was cooled to room temperature and the
pH adjusted to 6.3 with aqueous sodium hydroxide. The
resultant solids content was 11.58% (w/w). Subsequent
batches had inherent viscosities in the range 2-3 but
viscosities as low as 0.15 measured at 25 C in 1 N sodium
chloride are acceptable.
Dry-Operative Multilayer Sodium and Potassium Ion-
Selective Electrodes
Dry-operative slide-format multilayer ion-selective
electrodes for the determination of potassium and sodium
were prepared to illustrate the present invention. The
invention is not limited to slide-format multilayer ISE's,
but can be used with other dry-operative electrode
configurations, such as bulb-type or capillary-flow type
CDS-181
CA 02319987 2000-09-20
- 16 -
electrodes. Nor is it intended to limit the invention to
electrodes selective only for potassium or sodium ions.
Comparative dry-operative multilayer ion-selective
electrodes comprising either gelatin or polymer A as
binder were prepared essentially as described in U.S.
Patents 4,053,381 and 4,214,968. The ion-selective
carrier for potassium was valinomycin and the carrier for
sodium was methyl monensin.
A schematic diagram of a dry-operative multilayer ISE
as employed in the examples is shown below:
poly(vinyl chloride-co-vinyl acetate)
(90/10) hydrophobic polymer overcoat
and ion-selective carrier
sodium or potassium chloride in gelatin
or Polymer A
-----------------------------------
silver chloride
-----------------------------------
silver
////polyethyleneteraphthalate support///////
The segmented lines are used to signify that metallic
silver, silver chloride and water-soluble sodium or
potassium salt and binder are combined in intimate contact
with each other, although generally not coated
simultaneously. The hydrophobic layer is in intimate
contact with the layer comprising the reference electrode,
but no substantial mixing of the layers occurs, which is
CDS-181
CA 02319987 2000-09-20
- 17 -
symbolized by the continuous line separating the two
layers.
Example 2
s ISE Keeping
Significant improvements in keeping stability of dry-
operative ion-selective electrodes under variable
environmental conditions were achieved using the
copolymers of the invention as binder.
Table 1 shows the potassium concentrations determined
using prepared aqueous solutions of known potassium
concentration containing 70 mg/mL bovine serum albumin.
Each data point represents the mean of three replicate
is measurements using electrodes prepared with either gelatin
or polymer A as binder, maintained at 15% relative
humidity (RH) and 70 F and compared with identically
prepared control ISE's, maintained at 33% RH in a freezer.
TABLE 1
Potassium Bias (mM) Bias (mM)
Concentration Polymer A Gelatin
(mM) 1 Wk 2 Wk 4Wk 1 Wk 2 Wk 4 Wk
2.0 -.005 .001 .001 NA NA -.01
3.8 .001 -.001 .002 -.012 -.015 -.020
5.3 -.006 -.005 -.004 -.017 -.018 -.021
6.0 .010 .008 .006 .032 .038 .041
9.2 .011 .008 .005 .056 .058 .060
NA = Not Available
CDS-181
= CA 02319987 2000-09-20
- 18 -
After one week at 15% RH there is a significant
change in performance of the potassium ISE prepared with
gelatin as binder. With polymer A as binder, the
estimated concentrations of potassium do not differ
significantly from that of the fresh ISE at 33% RH even
after 4 weeks at 15% RH.
Exainple 3
First Slide Bias
First-slide bias is a storage-related effect wherein
the first ISE slide element selected from a cartridge
container yields a significantly different measurement of
_ ion activity or concentration compared with the remaining
ISE slide elements from the same container.
Table 2 displays the first-slide bias observed, using
potassium ISE's prepared with either gelatin or polymer A,
that were stored in their containers for three days at
-- three different relative humidities at 70 F. Using a
single level of potassium in aqueous bovine serum albumin,
the bias was calculated by subtracting the mean of 2 to 10
replicate measurements obtained using slides 2 through 9
in a cartridge from the first slide of a cartridge.
CDS-181
CA 02319987 2000-09-20
- 19 -
Table 2
Percent Bias (mM) Bias (mM)
Relative Humidity Polymer A Gelatin
15 .04 .05
33 .08 .07
50 .12 .26
The first-slide bias observed at 50% RH is reduced
significantly with polymer A as binder compared with
gelatin as binder in the prior art electrode.
Example 4
On Analyzer Stability
Table 3 shows the departure from concentrations of
sodium obtained using electrodes kept on analyzer compared
with electrodes kept in a freezer (freezer control). The
electrodes were conditioned, that is, maintained at 22 C
at 33% relative humidity, for 7 days prior to packaging.
Table 3
Sodium Bias(mM) Bias(mM)
Concentration Polymer A Gelatin
(mM) 1 Wk 2 Wk 4Wk 1 Wk 2 Wk 4Wk
95 -0.45 -0.50 -0.60 -0.10 -0.10 -2.00
145 -0.45 -0.45 -0.50 -0.10 0.10 -3.30
195 -0.35 -0.55 -0.65 1.30 1.60 -3.70
Table 4 shows the change in the percent coefficient
of variation (%CV) calculated from the data in Table 3.
CDS-181
= CA 02319987 2000-09-20
- 20 -
Table 4
Concentration Percent CV Percent CV
(mM) Polymer A Standard Formula
1 Wk 2 Wk 4Wk 1 Wk 2 Wk 4 Wk
95 .39 .45 .54 .46 .51 1.38
145 .26 .22 .39 .58 .67 .92
195 .32 .29 .44 .65 .46 1.7
Tables 5 and 6 show similar results for identical
sodium electrodes prepared with polymer A as binder except
the electrodes were not preconditioned prior to packaging.
Table 5
Concentration Bias from Freezer Control (mM)
(mM) 1 Wk 2 Wk 4 Wk
95 -.50 -.20 -.60
145 -.90 -.70 -1.05
195 -.30 .50 -.50
Table 6
Concentration Percent CV
(mM) 1 Wk 2 Wk 4 Wk
95 .72 ..55 .32
145 .68 .57 .50
195 .68 .31 .77
Sodium ISE's comprising polymer A as binder in the
electrolyte layer are significantly more robust under
environmental variations compared with prior art sodium
ISE's prepared with gelatin as binder.
CDS-181
CA 02319987 2006-11-30
- 21 -
In general, the polymeric compositions of the present
invention, when used as binder for the internal reference
electrode in dry-operative ISE's provide the following
advantages: reduced brittleness, improved adherence to
the hydrophobic overcoat, less susceptibility to
variations in ambient humidity, compatibility with
concentrations of water-soluble salt up to 1 molar, and
ISE's having improved performance.
The present invention has been described in detail
with respect to particular preferred embodiments. It will
be understood that variations and modifications can be
effected without departing from the scope and spirit of
the invention.
CDS-181
